1MDW
Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation
Summary for 1MDW
| Entry DOI | 10.2210/pdb1mdw/pdb |
| Related | 1AJ5 1ALW 1DFO 1KFU 1KFX 1KXR |
| Descriptor | Calpain II, catalytic subunit, CALCIUM ION (3 entities in total) |
| Functional Keywords | calpain cysteine protease fold, two cooperative calcium sites, helix instability, tryptophan-based active site blockage, hydrolase |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cytoplasm (By similarity): Q07009 |
| Total number of polymer chains | 2 |
| Total formula weight | 73776.27 |
| Authors | Moldoveanu, T.,Hosfield, C.M.,Lim, D.,Jia, Z.,Davies, P.L. (deposition date: 2002-08-07, release date: 2003-04-29, Last modification date: 2024-02-14) |
| Primary citation | Moldoveanu, T.,Hosfield, C.M.,Lim, D.,Jia, Z.,Davies, P.L. Calpain silencing by a reversible intrinsic mechanism. Nat.Struct.Biol., 10:371-378, 2003 Cited by PubMed Abstract: Uncontrolled activation of calpain can lead to necrotic cell death and irreversible tissue damage. We have discovered an intrinsic mechanism whereby the autolysis-generated protease core fragment of calpain is inactivated through the inherent instability of a key alpha-helix. This auto-inactivation state was captured by the 1.9 A Ca(2+)-bound structure of the protease core from m-calpain, and sequence alignments suggest that it applies to about half of the calpain isoforms. Intact calpain large subunits are also subject to this inhibition, which can be prevented through assembly of the heterodimers. Other isoforms or their released cores are not silenced by this mechanism and might contribute to calpain patho-physiologies. PubMed: 12665854DOI: 10.1038/nsb917 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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